NeuroScience_LEC - Development of CNS

Neuro-embryology

T or F: Brain development occurs in a sequential manner

False, it is in an orderly manner

Development of Nervous System

The NS develops between week ___ and _____

The brain becomes an organ weighing ____ g at birth, ____ at 6 yrs old and _____ in adulthood

__ % of births are associated with major malformations of the CNS

___% of spontaneously aborted fetuses & __% of infants who die within the 1st yr of life have major CNS malformations.

4 and adulthood

800g;1200g;1400g

3%

75%, 40%

Manifestations of Human embryogenesis

Bone retardation

Malformation

functional defect

retardation

(1) Pre - embryonic Period (Conceptus)

____ weeks

• zygote are dividing that will form bi-laminar embryo

• this stage is NOT susceptible to _______ ( malformation)

• _______ are common when development does not proceed accordingly

first 2 weeks

teratogenesis

pre-natal death

(2) Embryonic Development

___- ___ weeks

• Major _ can possibly come to the picture

3-8 weeks

morphological abnormalities

(3) Fetal Period

___ - ___ weeks

• functional defects, growth retardation, minor abnormalities

9-38 weeks

______

• formation of trilaminar from bilaminar disc (week __)

• embryo transforms from 1D layer of epithelial cells (blastula) to multi layer structure called ____

• Zygote → blastomere→ morula → blastocyst→ blastula

• This stage is where ectoderm, mesoderm & endoderm starts to form ( primary germ layers)

Gastrulation

gastrula

3rd week ( neural tissues appears)

Gastrulation Period

Mesoderm develops into _______

ectoderm develops into ________

endoderm develops into _______

muscles, blood vessels, organs, bone marrow

CNS,PNS & skin

lungs, liver & gut

Embryonic Development

______ - establishes the basic body plan of all vertebrates( midline axis, bilat. symmetry, rostral (head) and caudal ends & dorsal and ventral surfaces)

_______ - defines the rostral direction (papunta sa taas); as the node regresses, a notochordal process develops in the area rostral to it and somites begin to form on either side of the notochord

_______ - induces epiblast cells to form neuro-ectodorm

Primitive streak

Primitive node/ Hensen’s node

Notochord

Embryonic Development

_______ - a process of cell to cell signaling by which the underlying mesoderm induces the ectoderm to become neuro-ectoderm & form the neural plate, giving rise to most of the nervous system. This is due to the actions of hormones, neurotransmitters and growth factors.

This takes place in the _____ of the head process overlying the notochord

Starts about the ___-___ day of intrauterine life

Neural Induction

ectoderm

16-17th day

Embryonic Development

_____ Arises from the axial mesoderm ( day __ to week)

• Directs the overlying ectoderm to form the neural plate : Induction ( noggin & chordin)

• Defines the longitudinal axis of the embryo ( by production of cell adhesion molecules)

• Determines the orientation of the vertebral column

• Persists as the nucleus pulposus of the IVD

Notochord

16th to 4 week

Embryonic Development

______ is a slipper shaped plate of thickened ectoderm

• located in the mid dorsal region in front of the primitive gut

• lateral edges become elevated to form neural folds

• This is developed at day ____ while ____ for the neural folds

• At about __ day the neural folds are in contact with each other. It become more elevated, approach each other in the midline and fuse to form the neural tube

Neural plate

day 18 , day 20

day 21

Embryonic Development

Once the neural tube is closed, it begins in the cranio-caudal (head-tail) extent of nervous system. This happens during day ___ & ___

Day 21 and 22

Embryonic Development: Primitive Streak

Emerges as a groove at the ___ part of the embryo with the primitive node at the ____ ( 19 days) . Epiblast cells moving to the primitive streak now form ____ again.

A thickening of ____ forms the neural plate, initiated at the cranial pole. The primitive streak initiates the _____ . At 20 days of gastrulation, the neural folds will elevated to form neural plate and holes will be closing to form neural tube.At day 20 also , you can see the ____ which support the elevation of neural folds and precursors of vertebrae

caudal (tail); cranial (head)

3 germs layers again; ectoderm, mesoderm and endoderm

ectoderm

gastrulation

somite

Embryonic Development

Closure of the neural tube proceeds ______ ( both sides sabay nagsasara)

Fusion begins at the ___ of the developing neural tube and proceeds at a manner of a double headed zipper. The unclose cephalic and caudal portion are called _______ .During the process, the lumen/ opening of neural tube is open to the amniotic cavity both above and below. The anterior neuropore will close at ___ days of gestation while ___ for posterior neuropore. The distances from the cervical region being unequal.

bidirectionally

center

anterior and posterior neuropore

24 days ;26 days

Embryonic Development: Neurulation

_______ a process by which the neural plate folds over on itself and fuses in a zipper-like fashion to become a neural tube

Types:

_______ - the process by which the brain & most (cervical, thoracic, UPPER lumbar ) of the spinal cord are formed

Begins when the notochord induces the overlying embryonic ectoderm to form a neural plate ___ and ends by ___

Neurulation

Primary Neurulation

Day 18

Day 28

Embryonic Development: Neurulation

_____ - the process by which the caudal parts of the spinal cord (lower lumbar, sacral, & coccygeal segments) are formed.(Day __ to _)

_____ -On day 20, a mass of mesenchyme cells that develop in the caudal part of the neural tube and it enlarges eventually becomes continuous with the neural tube formed with the primary neurulation by day ____

Secondary Neurulation ( day 20 - 42)

Caudal eminence

day 40

Embryonic Development: Primary vs Secondary Neurulation

Primary Neurulation starts at the ______ and forms its ____ while Secondary Neurulation starts at _____ condenses and hallows to undergo ________.

Primary Neurolation undergoes _____/folding while Secondary Neurolation consists of _____ of solid epithelial cells in tail of emrbyo.

ectoderm → tube

mesenchyme → mesenchymal condensation

rolling/folding ; cavitation

Neural Tube Related Birth Defects

_______ - failure to close of Anterior neuralpore; Occurs more in Females

_______ - failure to close posterior neuralpore

Anencephaly ( brain is not formed, meninges maybe absent, neonatal death, defect is from lamina terminalis to foramen magnum ; 5:10,000; folic acid prevents this)

Spina bifida

Dysraphic Defects = Defective Primary Neurulation

Anterior Neuropore : Anencephaly, ___ & _____

Posterior Neuropore: ___, _____ & ____

Encephalocoele, Chiari I malformation

Spina bifida occulta, aperta and cystica

Dysraphic Defects = Defective Primary Neurulation

_____ - Disorder of dorsal induction

______ - minor fusion failure of the post. vertebral arches unaccompanied by herniation of meninges or neural tissue

______ - collectively designates meningocele, myelomemeningoele and other cystic lesions

Spinal Dysraphism

Spina bifida occulta

Spina bifida cystica

Primary Brain Vesicles

The rostral end of the neural tube undergoes _______ giving rise to 3 primary brain vesicles which are ____(3) at week ____

_____ flexure is also formed at the spinal cord or rhombencephalon junction and ____ flexure at the level of mesencephalon

Between the 4th and 8th weeks, the brain tube folds sharply at 3 locations: (1) _____, (2) ______ (3) _______

Cephalization

Prosencephalon (forebrain) , mesencephalon ( midbrain) , rhombencephalon (hindbrain) at Week 4

cervical flexure and mesencephalic (cephalic)

mesencephalic (cephalic) flexure , cervical flexure & , pontine flexure

Further Subdivisions of the Brain Vesicles

During the __ week, the 3 primary vesicles divide into 5 secondary brain vesicles.

___ flexure is now present due to equal growth of both cervical and cephalic flexure.( Located in between metencephalon & myelencephalon)

____ forms as out pocketing of the forebrain (telencephalic vesicles) and expands with complex lobes ,gia and sulci to be later called as ______ (largest part of the brain)

5th week

pontine flexure

telencephalon → cerebrum

Further Subdivisions of the Brain Vesicles (Week 5)

Primordial to cerebral hemispheres is _____

Main structures of the forebrain develop during ___ month of gestation; mesoderm is simultaneously forming facial structures and abnormalities are associated with facial defects.

________ is the process of forebrain development

The pontine flexure divides the hindbrain into ______ rostrally and ____ caudally.

telencephalic vesicles

2nd month

ventral induction

metencephalon (pons) & myelencephalon (medulla)

Further Subdivisions of the Brain Vesicles

Telencephalon Adult derivates: ____ cortex, ____ white matter (internal capsule - olfactory bulb ), portions of basal ganglia, amygdala and hippocampus

_______ divides to thalami nuclei and gives rise to optic cap → optic nerve and retina

cerebral and subcortical

Diencephalon

Diagnose

A congenital disgenesis of diencephalon with hypoplasia of optic nerve , thalamus and pitituary gland and other midline defects. Accompanied with the absence of septum pellusidum and agenesis of corpus calosum

Septoptic dysplasia

Ventricular System

The cavities of the telocephalic vesicles become the ___ ventricles

The diacephalic cavity becomes the ______ ventricle

The cavity of the mesencephalon becomes the narrow _______

The rhomben cephalic vesicles becomes the _____ ventricle

lateral

4th

cerebral aqueduct

Ventricular System

The opening between the lateral and 3rd ventricle becomes _______

Openings that arise in the caudal root of 4th ventricle during development form communication with ventricular system and subacharanoid space which are _____ and paired __________

intraventricular foramina ( Foramen of Monro)

foramen of magendi and paired lateral foramina of luschka

Ventricular System

CSF is produce mainly by the ___ and _____. It passes to the subarachnoid space and from there it is absorbed to the venous system through the ________ located primarily in the superior sagittal plane.

choroid plexuses of the lateral and 3rd venticles

arachnoid villi

Ventricular System

The lumen (opening) of ______ persists as the ventricular system of the adult brain

Choroid plexus develops where ______ and ______ are in direct contact

lumen of neural tube

pia mater and ependyma

Ventricular System

The ventricular system is lined by ______. Each ventricle has a thin root composing of an internal layer of _____ and ______ ( outer layer). In each ventricle, blood vessels invaginate to form ______ which eventually produces ______

ependymal cells

ependyma and pia matter

choroid plexus → CSF

Ventricular System

If there is problem in formation of ventricular system, ___________ happens. Caused by obstruction of flow of CSF during prenatal development. Ventricular system is dilated.

The ___________ is a site for blockage. This can be associated with ________ which is inherited and isolated associated with CSF deformities.

Congenital Hydrocephalus

cerebral acqueduct

Congenital atresia of Acqueduct

Neuronal Proliferation

Peak time period: ___ months

Major Events:

Stage 1 : ______ and ______ zone are sites of neuronal cell proliferation

Stage 2 : _______ units are produced by symmetrical divisions of stem cells

Stage 3 :Proliferative units later enlarge by _______ divisions of the stem cells before migration

3-4 months

Ventricular zone and subventricular zone

Proliferative units

asymmetrical

Neuronal Proliferation

________ multiply in the periventricular region producing neuroblasts & glioblasts

Blast cells

Embryonic Development

________ will give rise to neuron and neuroglia

Periventricular Neuroepithelium

Periventricular Neuroepithelium

_____ → _____→ ______ → _____ to Neuron

______ → _____ → ______→______ → Astrocytes/ Oligodendrocytes & radial glial cells

Apolar , bipolar, unipolar & multipolar Neuroblasts

Primitive, bipolar, unipolar glioblast and astroblast/oligodendroblast & radial glial progenitor

Neuronal Migration ( After cell proliferation)

As the cells undergo last division, they begin to migrate away from the luminal ventricular surface of the periventricular area of the transient glial cells. This will guide migration of neurons, called______. As they migrate they formed moving cell bodies between the marginal and ventricular zones called intermediate zones.

Radial glial cells

Neuronal Migration

Peak period: _______

Major events:

Cerebrum

Radial migration of cells forms ____ and _____ (basal ganglia)

Cerebellum

Radial migration of cells forms ______ and _______

Tangential migration of _______& _____ granule cells

3-5 months

cerebral cortex and deep nuclei

Purkinje cells and dental nuclei

external & internal granule cells

Neuronal Migration

Radial migration accounts for bulk of ______. Neurons that makes up our cerebral hemisphere.

cortical neurons

Neuronal Migration

During embryogenis, as proliferation in the neuro epithelium thicken the cortical wall. A system of radial glial fibers will cross the radial plane and each has its soma in the ventricular zone and elaborates a process of bonds the wall of neural tube and reaches the surface that would be anchored to the basal membrane. Basically, making out the _______ of _____

thickness of cerebral cortex

Neuronal Migration

Neurons will then reach final destination by climbing along glial cells particularly _______. The migrating neurons use this as their main highway to migrate.

radial glial cells

Differentiation of Axon & Dendrite

Once the neuron migrated it can be _______ or ______.

The number of neurons that underwent apoptosis is ____

The development of axons is facilitated by ________ ( slope structures that form at the edge of an axon). These axons will go to their targets or away from others

Formation of dendrites occur by ________ pattern.

mature neuron (complete parts) or apoptosis

40%

neuronal growth cones

calcium regulated transmission pattern

Synaptogenesis

______ development of synapses ( Not all synapses will be functional)

_____ point of contact between 2 neurons.

First synapse are observed at about _______ week of gestation while peak of production occurs in ______

________ is the process of synaptic reduction. Dependent process of experience and learning in life. Eliminating excess synapses. At first (synaptogenesis) it is gene driven but once brain achieves synapse pruning(synapses eliminated)., balance shifts to being experience/learning driven .

Synaptogenesis ; synapse

23rd week (2nd trimester) → 1st year

Synaptic pruning

Myelination

Final stage of human embryonic development would be ________. The process where axons are wrapped with schwann and oligodendrocytes. Insulation of axons allows them to transmit electrical signals faster.

Timing of myelination depends on the region of the brain in which it occurs. Some myelination occurs earlier especially in _____ and _____ areas ( complete around preschool period). In contrast, higher cognitive abilities like pre-frontal cortex is not complete until _______

Myelination

sensory and motor areas

adolescence

Brain Development

Brain development starts a few weeks after ______ and completes in ______

The basic structure of the brain is laid down primarily during the pre-natal period and early childhood while formation and refinement will continue throughout life. Many brain functions will not develop in the same pace nor the pattern follows the same time frame.

conception → early adulthood

Even after neuronal injury,

You have the capacity to restore neuronal function 😉 - Dr. Lokin